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Updated: May 27, 2025

Assays for Validating Histone Acetyltransferase Inhibitors

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

The histone deacetylase inhibitor Scriptaid targets G-quadruplexes.

Victoria Sanchez-Martin^1,2,3,4, Dusan Ruzic⁵, Maria J Tello-Lopez^1,6

¹GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Granada 18016, Spain.

|February 18, 2025

Summary

Scriptaid, a histone deacetylase inhibitor, shows anti-cancer effects by targeting G-quadruplexes (G4s) in colorectal cancer cells. This interaction disrupts cell cycle and transcription, revealing a new mechanism for Scriptaid

Keywords:

G-quadruplex RNA polymerase I colorectal cancer histone deacetylase inhibitor transcription

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Area of Science:

Biochemistry
Molecular Biology
Cancer Research

Background:

Scriptaid is a known histone deacetylase inhibitor with anti-tumoural properties.
Its potential interaction with G-quadruplexes (G4s), despite structural similarities to known G4 ligands, remained unexplored.

Purpose of the Study:

To investigate the cytotoxic activity and biological effects of Scriptaid in colorectal cancer (CRC) models.
To identify and characterize the G-quadruplex (G4) targets of Scriptaid.

Main Methods:

Synthesis of Scriptaid and screening of its cytotoxic activity in CRC cell lines.
Evaluation of biological activity using cell cycle analysis, immunofluorescence, qRT-PCR, and Western blot.
Identification of G4 targets through various binding assays.

Main Results:

Scriptaid demonstrated significant cytotoxicity, induced cell cycle arrest, and caused nucleolar stress in CRC cells.
The compound impaired RNA polymerase I (Pol I) transcription, stabilized G4 structures, and led to DNA damage.
Binding assays confirmed Scriptaid interacts with G4s located in ribosomal DNA.

Conclusions:

Scriptaid's anti-cancer effects in CRC are mediated by its interaction with G-quadruplexes (G4s) in ribosomal DNA.
This interaction disrupts crucial cellular processes including transcription and DNA integrity.
The study reveals G4 binding as a primary mechanism of action for Scriptaid in human cells.